title: Type IV pilus of Pseudomonas aeruginosa confers resistance to antimicrobial activities of the pulmonary surfactant protein-A.
abstract: Pseudomonas aeruginosa(PA) is a Gram-negative bacterial pathogen commonly associated with chronic lung infections. Previously, we have identified several PA virulence factors that are important for resistance to the surfactant protein-A (SP-A), a pulmonary innate immunity protein that mediates bacterial opsonization and membrane permeabilization. In this study, we demonstrate that the type IV pilus (Tfp) is important in the resistance of PA to the antibacterial effects of SP-A. The Tfp-deficient mutant ΔpilA is severely attenuated in an acute pneumonia model of infection in the lungs of wild-type mice, but is virulent in the lungs of SP-A(-/-) mice. The ΔpilA bacteria are more susceptible to SP-A-mediated aggregation and opsonization. In addition, the integrity of the outer membranes of ΔpilA bacteria is compromised, rendering them more susceptible to SP-A-mediated membrane permeabilization. By comparing Tfp extension and retraction mutants, we demonstrate that the increased susceptibility of ΔpilA to SP-A-mediated opsonization requires the total absence of Tfp from PA cells. Finally, we provide evidence of increased expression of nonpilus adhesin OprH that may serve as an SP-A ligand, resulting in increased phagocytosis and preferential pulmonary clearance of ΔpilA.
authors.affiliation: Department of Pathobiology, University of Illinois at Urbana-Champaign, Urbana, Ill., USA.
authors.forename: Rommel Max
authors.initials: RM
authors.lastname: Tan
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Kuang
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Hao
authors.forename: Gee W
authors.initials: GW
authors.lastname: Lau
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000235:genetics / Q000276:immunology; D036781:Fimbriae Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D008024:Ligands; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000276:immunology; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D010587:Phagocytosis / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D008024:Ligands; C402926:OprH protein, Pseudomonas aeruginosa; D037662:Pulmonary Surfactant-Associated Protein A; D037521:Virulence Factors; D036781:Fimbriae Proteins